Novel pharmacological effects of poly (ADP-ribose) polymerase inhibitor rucaparib on the lactate dehydrogenase pathway

Yuma Nonomiya, Kohji Noguchi, Kazuhiro Katayama, Yoshikazu Sugimoto

Research output: Contribution to journalArticle

Abstract

Poly (ADP-ribose) polymerases (PARPs) are involved in various cellular events, including DNA repair. PARP inhibitors including olaparib and rucaparib, have been specially developed against breast and ovarian cancers deficient in DNA repair systems. In this study, we found that PARP1-defective olaparib-resistant A2780 cells (ola-R cells) cells were still sensitive to two PARP inhibitors, rucaparib and veliparib. Metabolomic analysis revealed that rucaparib suppressed the lactate dehydrogenase (LDH)-mediated conversion of pyruvic acid to lactic acid in A2780 cells, although olaparib did not. The inhibition of LDH by siRNA-mediated knockdown or by LDH inhibitors suppressed the growth of ovarian cancer cells. Our results suggested that the suppression of the LDH-associated pathway contributed to the pharmacological effects of rucaparib.

Original languageEnglish
Pages (from-to)501-507
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume510
Issue number4
DOIs
Publication statusPublished - 2019 Mar 19

Fingerprint

L-Lactate Dehydrogenase
Pharmacology
Ovarian Neoplasms
Repair
DNA Repair-Deficiency Disorders
Growth Inhibitors
Metabolomics
Poly(ADP-ribose) Polymerases
DNA
Pyruvic Acid
DNA Repair
Small Interfering RNA
Lactic Acid
Cells
Breast Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
rucaparib
olaparib

Keywords

  • LDHA
  • Olaparib
  • Ovarian cancer
  • PARP1
  • Rucaparib

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Novel pharmacological effects of poly (ADP-ribose) polymerase inhibitor rucaparib on the lactate dehydrogenase pathway. / Nonomiya, Yuma; Noguchi, Kohji; Katayama, Kazuhiro; Sugimoto, Yoshikazu.

In: Biochemical and Biophysical Research Communications, Vol. 510, No. 4, 19.03.2019, p. 501-507.

Research output: Contribution to journalArticle

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